Certain cationic, amphiphilic drugs induce a phospholipid storage disorder when administered to animals and humans. The alveolar macrophage (AM) is particularly sensitive to this disorder. Following the induction of phospholipidosis in animals, the AMs accumulate in the alveoli, become markedly enlarged and show unusual ultrastructural changes. Because the AM plays such an important role in host pulmonary defense, it is the objective of this project to determine if changes occur in AM function as a result of the induction of this disorder. The proposed research will focus on two aspects of this problem: (a) We will examine whether the AMs from rats treated with the phospholipidosis-inducing drug, chlorphentermine are more susceptible to lipid peroxidation than normal AMs. Lipid peroxidation will be induced by cumeme hydroperoxide and cell viability will be assessed. (b) We have shown previously that AMs from chlorphentermine-treated rats release less reactive oxygen species than normal AMs when challenged with zymosan particles. We will now examine whether the adminstration of iprindole, another drug which causes phospholipidosis, results in the same phenomenon in AMs. Since the release of oxidizing species from AMs may be important in the microbicidal activity of these cells, this study will provide important information on this aspect of AM function.